tbuckley/cabot-search huggingface dataset:
Effect of Music Therapy on Parent-Infant Bonding Among Infants Born Preterm
Authors: Claire M. Ghetti, Tora Söderström Gaden, Łucja Bieleninik, Ingrid Kvestad, Jörg Assmus, Andreas Størksen Stordal, Luisa Fernanda Aristizabal Sanchez, Shmuel Arnon, Jeanette Dulsrud, Cochavit Elefant, Shulamit Epstein, Mark Ettenberger, Heidi Glosli, Ludwika Konieczna-Nowak, Marcela Lichtensztejn, Merethe Wolf Lindvall, Julie Mangersnes, Luz Dary Murcia Fernández, Catharina Janner Røed, Gladys Saá, Betty Van Roy, Bente Johanne Vederhus, Christian Gold
Journal: JAMA Network Open (2023)

Parent-infant bonding contributes to long-term infant health but may be disrupted by preterm birth.To determine if parent-led, infant-directed singing, supported by a music therapist and initiated in the neonatal intensive care unit (NICU), improves parent-infant bonding at 6 and 12 months.This randomized clinical trial was conducted in level III and IV NICUs in 5 countries between 2018 and 2022. Eligible participants were preterm infants (under 35 weeks' gestation) and their parents. Follow-up was conducted across 12 months (as part of the LongSTEP study) at home or in clinics. Final follow-up was conducted at 12 months' infant-corrected age. Data were analyzed from August 2022 to November 2022.Participants randomized to music therapy (MT) plus standard care or standard care alone during NICU admission, or to MT plus standard care or standard care alone postdischarge, using computer-generated randomization (ratio 1:1, block sizes of 2 or 4 varying randomly), stratified by site (51 allocated to MT NICU, 53 to MT postdischarge, 52 to both, and 50 to neither). MT consisted of parent-led, infant-directed singing tailored to infant responses and supported by a music therapist 3 times per week throughout hospitalization or 7 sessions across 6 months' postdischarge.Primary outcome was mother-infant bonding at 6 months' corrected age, measured by the Postpartum Bonding Questionnaire (PBQ), with follow-up at 12 months' corrected age, and analyzed intention-to-treat as group differences.Of 206 enrolled infants with 206 mothers (mean [SD] age, 33 [6] years) and 194 fathers (mean [SD] age, 36 [6] years) randomized at discharge, 196 (95.1%) completed assessments at 6 months and were analyzed. Estimated group effects for PBQ at 6 months' corrected age were 0.55 (95% CI, -2.20 to 3.30; P = .70) for MT in the NICU, 1.02 (95% CI, -1.72 to 3.76; P = .47) for MT postdischarge, and -0.20 (95% CI, -4.03 to 3.63; P = .92) for the interaction (12 months: MT in NICU, 0.17; 95% CI, -2.71 to 3.05; P = .91; MT postdischarge, 1.78; 95% CI, -1.13 to 4.70; P = .24; interaction, -1.68; 95% CI, -5.77 to 2.41; P = .42). There were no clinically important between-group differences for secondary variables.In this randomized clinical trial, parent-led, infant-directed singing did not have clinically important effects on mother-infant bonding, but was safe and well-accepted.ClinicalTrials.gov Identifier: NCT03564184.
DNA‐Templated Ag@Pd Nanoclusters for NIR‐II Photoacoustic Imaging‐Guided Photothermal‐Augmented Nanocatalytic Therapy
Authors: Ying Zhang, Yan Li, Jinyan Li, Fei Mu, Jing Wang, Chuang Shen, Hao Wang, Feng Huang, Bo Chen, Zhimin Luo, Lianhui Wang
Journal: Advanced Healthcare Materials (2023)

Abstract Developing multifunctional nanozymes with photothermal‐augmented enzyme‐like reaction dynamics in the second near‐infrared (NIR‐II) biowindow is of significance for nanocatalytic therapy (NCT). Herein, DNA‐templated Ag@Pd alloy nanoclusters (DNA‐Ag@Pd NCs) are prepared as a kind of novel noble‐metal alloy nanozymes by using cytosine‐rich hairpin‐shaped DNA structures as growth templates. DNA‐Ag@Pd NCs exhibit high photothermal conversion efficiency (59.32%) under 1270 nm laser and photothermally augmented peroxidase‐mimicking activity with synergetic enhancement between Ag and Pd. In addition, hairpin‐shaped DNA structures on the surface of DNA‐Ag@Pd NCs endow them with good stability and biocompatibility in vitro and in vivo, and enhanced permeability and retention effect at tumor sites. Upon intravenous injection, DNA‐Ag@Pd NCs demonstrate high‐contrast NIR‐II photoacoustic imaging‐guided efficient photothermal‐augmented NCT of gastric cancer. This work provides a strategy to synthesize versatile noble‐metal alloy nanozymes in a bioinspired way for highly efficient therapy of tumors.
Subsets of IFN Signaling Predict Response to Immune Checkpoint Blockade in Patients with Melanoma
Authors: Brooke Horowitch, Daniel Y. Lee, Min Ding, Sandra Martinez-Morilla, Thazin Nwe Aung, Feriel Ouerghi, Xueting Wang, Wei Wei, William Damsky, Mario Sznol, Harriet Kluger, David L. Rimm, Jeffrey J. Ishizuka
Journal: Clinical Cancer Research (2023)

Abstract Purpose: IFN signaling in the tumor microenvironment is a critical determinant of both response and resistance of cancer to immune checkpoint inhibitors (ICI). We hypothesized that distinct patterns of IFN signaling in melanoma are associated with clinical response or resistance to ICIs. Experimental Design: Two tissue microarrays containing samples from 97 patients with metastatic melanoma who received nivolumab, pembrolizumab, or a combination of ipilimumab and nivolumab at Yale New Haven Hospital between 2011 and 2017 were randomized into discovery and validation cohorts. Samples were stained and visualized using multiplexed immunofluorescence microscopy for STAT1, STAT1 phosphorylated at Y701 (pSTAT1Y701), and PD-L1, and signals were quantified using the automated quantitative analysis method of quantitative immunofluorescence. Treatment response was assessed using RECIST, and overall survival was analyzed. For in vitro studies, human melanoma cell lines were stimulated with IFNγ and IFNβ, and Western blotting was performed. Results: Pretreatment STAT1 levels were higher in responders to ICIs [complete response/partial response/stable disease (SD) for &amp;gt; 6 months] than in nonresponders (SD &amp;lt; 6 months/progressive disease). Higher pretreatment STAT1 levels were associated with improved survival after ICIs in both the discovery and validation cohorts. Western blot analysis of human melanoma cell lines stimulated with IFN demonstrated distinct patterns of upregulation of STAT1 compared with pSTAT1Y701 and PD-L1. When combining STAT1 and PD-L1 markers, patients with STAT1highPD-L1low tumors had improved survival compared with those with STAT1lowPD-L1high tumors. Conclusions: STAT1 may better predict melanoma response to ICIs than current strategies, and combined STAT1 and PD-L1 biomarkers may provide insight into IFN-responsive versus IFN-resistant states.
Trends in the mortality, incidence and disability-adjusted life-years of appendicitis in EU15+ countries: an observational study of the Global Burden of Disease Database, 1990–2019
Authors: Dominic W. Proctor, Richard Goodall, Kim Borsky, Justin D. Salciccioli, Dominic C. Marshall, Kumaran Shanmugarajah, Abdulla Mohamed, Joseph Shalhoub
Journal: International Journal of Surgery (2023)

Appendicitis places a substantial burden on healthcare systems, with acute appendicitis alone being the most common abdominal surgical emergency worldwide. Further characterisation of the disease burden in EU15+ countries may help optimise the distribution of healthcare resources. The aim of this observational study was to assess the trends in mortality, incidence and disability-adjusted life-years (DALYs) of appendicitis across European Union (EU) 15+ countries between the years 1990 and 2019, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 .Age-standardised mortality rates (ASMRs), age-standardised incidence rates (ASIRs) and DALYs data for appendicitis in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. Temporal trends within the study period were analysed using Joinpoint regression analysis.The median ASMRs across EU15+ countries in 2019 were 0.08/100 000 and 0.13/100 000 for females and males, respectively. Between 1990 and 2019 the median percentage change in ASMR was -52.12% for females and -53.18% in males. The median ASIRs in 2019 for females and males were 251/100 000 and 278/100 000, respectively, with a median percentage change of +7.22% for females and +3.78% for males during the observation period. Decreasing trends in DALYs were observed over the 30-year study period, with median percentage changes of -23.57% and -33.81% for females and males, respectively, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 .Overall, a general trend of decreasing appendicitis ASMRs and DALYs was observed across EU15+ countries, despite small overall increases in appendicitis ASIRs, Supplemental Digital Content 3, http://links.lww.com/JS9/A589 . Variations in both diagnostic and management strategies over the study period are likely contributory to the changing trends.
Distinct Roles of DRP1 in Conventional and Alternative Mitophagy in Obesity Cardiomyopathy
Authors: Mingming Tong, Risa Mukai, Satvik Mareedu, Peiyong Zhai, Shin-ichi Oka, Chun-Yang Huang, Chiao-Po Hsu, Fawad A.K. Yousufzai, Luke Fritzky, Wataru Mizushima, Gopal J. Babu, Junichi Sadoshima
Journal: Circulation Research (2023)

Obesity induces cardiomyopathy characterized by hypertrophy and diastolic dysfunction. Whereas mitophagy mediated through an Atg7 (autophagy related 7)-dependent mechanism serves as an essential mechanism to maintain mitochondrial quality during the initial development of obesity cardiomyopathy, Rab9 (Ras-related protein Rab-9A)-dependent alternative mitophagy takes over the role during the chronic phase. Although it has been postulated that DRP1 (dynamin-related protein 1)-mediated mitochondrial fission and consequent separation of the damaged portions of mitochondria are essential for mitophagy, the involvement of DRP1 in mitophagy remains controversial. We investigated whether endogenous DRP1 is essential in mediating the 2 forms of mitophagy during high-fat diet (HFD)-induced obesity cardiomyopathy and, if so, what the underlying mechanisms are.
Association of Antifolate Response Signature Status and Clinical Activity of Pemetrexed-Platinum Chemotherapy in Non–Small Cell Lung Cancer: The Piedmont Study
Authors: Joel R. Eisner, Gregory M. Mayhew, James M. Davison, Kirk D. Beebe, Yoichiro Shibata, Yuelong Guo, Carol Farhangfar, Farhang Farhangfar, Joshua M. Uronis, Jeffrey M. Conroy, Michael V. Milburn, David Neil Hayes, Kathryn F. Mileham
Journal: Clinical Cancer Research (2023)

Abstract Purpose: The Piedmont study is a prospectively designed retrospective evaluation of a new 48-gene antifolate response signature (AF-PRS) in patients with locally advanced/metastatic nonsquamous (NS) non–small cell lung cancer (NSCLC) treated with pemetrexed-containing platinum doublet chemotherapy (PMX-PDC). The study tested the hypothesis that AF-PRS identifies patients with NS-NSCLC who have a higher likelihood of responding positively to PMX-PDC. The goal was to gather clinical evidence supporting AF-PRS as a potential diagnostic test. Experimental Design: Residual pretreatment FFPE tumor samples and clinical data were analyzed from 105 patients treated with first-line (1L) PMX-PDC. Ninety-five patients had sufficient RNA sequencing (RNA-seq) data quality and clinical annotation for inclusion in the analysis. Associations between AF-PRS status and associate genes and outcome measures including progression-free survival (PFS) and clinical response were evaluated. Results: Overall, 53% of patients were AF-PRS(+), which was associated with extended PFS, but not overall survival, versus AF-PRS(−) (16.6 months vs. 6.6 months; P = 0.025). In patients who were stage I to III patients at the time of treatment, PFS was further extended in AF-PRS(+) versus AF-PRS(−) (36.2 months vs. 9.3 months; P = 0.03). Complete response (CR) to therapy was noted in 14 of 95 patients. AF-PRS(+) preferentially selected a majority (79%) of CRs, which were evenly split between patients stage I to III (six of seven) and stage IV (five of seven) at the time of treatment. Conclusions: AF-PRS identified a significant population of patients with extended PFS and/or clinical response following PMX-PDC treatment. AF-PRS may be a useful diagnostic test for patients indicated for systemic chemotherapy, especially when determining the optimal PDC regimen for locally advanced disease.
Phase II Study of Docetaxel and Trametinib in Patients with <i>KRAS</i> Mutation Positive Recurrent Non–Small Cell Lung Cancer (NSCLC; SWOG S1507, NCT-02642042)
Authors: Shirish M. Gadgeel, Jieling Miao, Jonathan W. Riess, James Moon, Philip C. Mack, Gregory J. Gerstner, Timothy F. Burns, Asma Taj, Wallace L. Akerley, Konstantin H. Dragnev, Noel Laudi, Mary W. Redman, Jhanelle E. Gray, David R. Gandara, Karen Kelly
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Efficacy of MEK inhibitors in KRAS+ NSCLC may differ based on specific KRAS mutations and comutations. Our hypothesis was that docetaxel and trametinib would improve activity in KRAS+ NSCLC and specifically in KRAS G12C NSCLC. Patients and Methods: S1507 is a single-arm phase II study assessing the response rate (RR) with docetaxel plus trametinib in recurrent KRAS+ NSCLC and secondarily in the G12C subset. The accrual goal was 45 eligible patients, with at least 25 with G12C mutation. The design was two-stage design to rule out a 17% RR, within the overall population at the one-sided 3% level and within the G12C subset at the 5% level. Results: Between July 18, 2016, and March 15, 2018, 60 patients were enrolled with 53 eligible and 18 eligible in the G12C cohort. The RR was 34% [95% confidence interval (CI), 22–48] overall and 28% (95% CI, 10–53) in G12C. Median PFS and OS were 4.1 and 3.3 months and 10.9 and 8.8 months, overall and in the subset, respectively. Common toxicities were fatigue, diarrhea, nausea, rash, anemia, mucositis, and neutropenia. Among 26 patients with known status for TP53 (10+ve) and STK11 (5+ve), OS (HR, 2.85; 95% CI, 1.16–7.01), and RR (0% vs. 56%, P = 0.004) were worse in patients with TP53 mutated versus wild-type cancers. Conclusions: RRs were significantly improved in the overall population. Contrary to preclinical studies, the combination showed no improvement in efficacy in G12C patients. Comutations may influence therapeutic efficacy of KRAS directed therapies and are worthy of further evaluation. See related commentary by Cantor and Aggarwal, p. 3563
Functional screens refine height GWAS loci
Authors: Cheryl L. Ackert-Bicknell
Journal: Cell Genomics (2023)

Genome-wide association studies (GWASs) have demonstrated the complexity of human height. Baronas et al.1 used a high-throughput CRISPR screen to identify genes that participate in growth plate chondrocyte maturation as a functional follow-up and validation screen to refine loci and establish causality after GWASs.
LTBP4 Protects Against Renal Fibrosis via Mitochondrial and Vascular Impacts
Authors: Chi-Ting Su, Daniel H.W. See, Yue-Jhu Huang, Tzu-Ming Jao, Shin-Yun Liu, Chih-Yi Chou, Chun-Fu Lai, Wei-Chou Lin, Chih-Yuan Wang, Jenq-Wen Huang, Kuan-Yu Hung
Journal: Circulation Research (2023)

As a part of natural disease progression, acute kidney injury (AKI) can develop into chronic kidney disease via renal fibrosis and inflammation. LTBP4 (latent transforming growth factor beta binding protein 4) regulates transforming growth factor beta, which plays a role in renal fibrosis pathogenesis. We previously investigated the role of LTBP4 in chronic kidney disease. Here, we examined the role of LTBP4 in AKI.LTBP4 expression was evaluated in human renal tissues, obtained from healthy individuals and patients with AKI, using immunohistochemistry. LTBP4 was knocked down in both C57BL/6 mice and human renal proximal tubular cell line HK-2. AKI was induced in mice and HK-2 cells using ischemia-reperfusion injury and hypoxia, respectively. Mitochondrial division inhibitor 1, an inhibitor of DRP1 (dynamin-related protein 1), was used to reduce mitochondrial fragmentation. Gene and protein expression were then examined to assess inflammation and fibrosis. The results of bioenergetic studies for mitochondrial function, oxidative stress, and angiogenesis were assessed.LTBP4 expression was upregulated in the renal tissues of patients with AKI. Ltbp4-knockdown mice showed increased renal tissue injury and mitochondrial fragmentation after ischemia-reperfusion injury, as well as increased inflammation, oxidative stress, and fibrosis, and decreased angiogenesis. in vitro studies using HK-2 cells revealed similar results. The energy profiles of Ltbp4-deficient mice and LTBP4-deficient HK-2 cells indicated decreased ATP production. LTBP4-deficient HK-2 cells exhibited decreased mitochondrial respiration and glycolysis. Human aortic endothelial cells and human umbilical vein endothelial cells exhibited decreased angiogenesis when treated with LTBP4-knockdown conditioned media. Mitochondrial division inhibitor 1 treatment ameliorated inflammation, oxidative stress, and fibrosis in mice and decreased inflammation and oxidative stress in HK-2 cells.Our study is the first to demonstrate that LTBP4 deficiency increases AKI severity, consequently leading to chronic kidney disease. Potential therapies focusing on LTBP4-associated angiogenesis and LTBP4-regulated DRP1-dependent mitochondrial division are relevant to renal injury.
A Biomimetic Nanoparticle Exerting Protection against Acute Liver Failure by Suppressing CYP2E1 Activity and Scavenging Excessive ROS
Authors: Qing Yao, Yingying Tang, Sheng Dai, Lihui Huang, Zewei Jiang, Shiming Zheng, Meng Sun, Yitianhe Xu, Ruijie Lu, Tuyue Sun, Huirong Huang, Xinyu Jiang, Xiaomin Yao, Guangyong Lin, Longfa Kou, Ruijie Chen
Journal: Advanced Healthcare Materials (2023)

Acute liver failure (ALF) is a severe liver disease caused by many reasons. One of them is the overdosed acetaminophen (APAP), which is metabolized into N-acetyl-p-benzoquinone imine (NAPQI), an excessive toxic metabolite, by CYP2E1, resulting in excessive reactive oxygen species (ROS), exhausted glutathione (GSH), and thereafter hepatocyte necrosis. N-acetylcysteine is the Food and Drug Administration-approved drug for detoxification of APAP, but it has limited clinical application due to the short therapeutic time window and concentration-related adverse effects. In this study, a carrier-free and bilirubin dotted nanoparticle (B/BG@N) is developed, which is formed using bilirubin and 18β-Glycyrrhetinic acid, and bovine serum albumin (BSA) is then adsorbed to mimic the in vivo behavior of the conjugated bilirubin for hitchhiking. The results demonstrate that B/BG@N can effectively reduce the production of NAPQI as well as exhibit antioxidant effects against intracellular oxidative stress via regulating the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signal axis and reducing the production of inflammatory factors. In vivo study shows that B/BG@N can effectively improve the clinical symptom of the mice model. This study suggests that B/BG@N own increases circulation half-life, improves accumulation in the liver, and dual detoxification, providing a promising strategy for clinical ALF treatment.
Positive End-Expiratory Pressure Deescalation in COVID-19–induced Acute Respiratory Distress Syndrome Unloads the Right Ventricle, Improving Hemodynamics and Oxygenation
Authors: Vasiliki Tsolaki, George E. Zakynthinos, John Papanikolaou, Nikitas Karavidas, Vasileios Vazgiourakis, Maria Eirini Papadonta, Paris Zygoulis, Ioannis Pantazopoulos, Demosthenes Makris, Epaminondas Zakynthinos
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"PEEP De-Escalation in Covid-19-induced Acute Respiratory Distress Syndrome Unloads the Right Ventricle Improving Hemodynamics and Oxygenation." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML
Authors: Armin Rashidi, Maryam Ebadi, Tauseef Ur Rehman, Heba Elhusseini, David Kazadi, Hossam Halaweish, Mohammad H. Khan, Andrea Hoeschen, Qing Cao, Xianghua Luo, Amanda J. Kabage, Sharon Lopez, Shernan G. Holtan, Daniel J. Weisdorf, Alexander Khoruts, Christopher Staley
Journal: Journal of Clinical Oncology (2023)

PURPOSE Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial. METHODS Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months. RESULTS In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister. CONCLUSION In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials.